Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma☆

Background/Aims

Hepatitis B virus (HBV) levels correlate with the development of hepatocellular carcinoma (HCC), but the role of viral load in HCC recurrence after tumor resection remains unclear. Herein we aimed to investigate the role of viral load in HCC recurrence following tumor resection.

Methods

From 1990 to 2002, 193 HBV-related HCC patients who underwent tumor resection in Taipei Veterans General Hospital were enrolled. Serum HBV DNA level and mutations were analyzed for association with early and late recurrence, together with other clinical variables.

Results

During a follow-up of 58.2±44 months, 134 patients had HCC recurrence. Multivariate analysis showed that multinodularity (Hazard ratio [HR], 95% confidence interval [CI]; 2.232, 1.021–4.878), macroscopic venous invasion (4.693, 1.645–13.391), AFP >20ng/ml (3.891, 1.795–8.475), and cut margin ⩽1cm (3.333, 1.487–7.470) were correlated with early recurrence (within two years of operation) of HCC. In addition, multivariate analysis determined that Ishak hepatic inflammatory activity >6 (4.658, 1.970–11.017), multinodularity (3.266, 1.417–7.526), ICG-15 >10% (2.487, 1.095–5.650) and HBV DNA level >10⁶ copies/ml (2.548, 1.040–6.240) were significantly associated with late recurrence (>two years after resection). Patients with high viral loads tended to have higher Ishak inflammatory (7.00±3.07 vs. 5.33±2.96, p=0.001) and fibrosis scores (4.17±2.01 vs. 3.20±2.41, p=0.007) than those with lower loads.

Conclusions

Tumor factors were associated with early HCC recurrence while high viral loads and hepatic inflammatory activity were associated with late recurrence. Pre- and post-operative antiviral and anti-inflammatory therapies may be crucial in reducing late recurrence.

Abbreviations: HBV, hepatitis B virus, HCC, hepatocellular carcinoma, HR, Hazard ratio, CI, confidence intervals, HCV, hepatitis C virus, ICG, indocyanine green, BCP, basic core promoter, IRB, institutional review board, HBsAg, hepatitis B surface antigen, anti-HBe, antibody against HBeAg, ALT, alanine aminotransferase, AST, aspartase aminotransferase, AFP, alfa-fetoprotein, GGT, gamma-glutamyltransferase, BUN, blood urea nitrogen, Alk-P, alkaline phosphatase, PCR-RFLP, PCR restriction fragment length polymorphism, ICG-15, indocyanine green dye intravenously injected at 15min

Keywords: Genotype, Hepatitis B viral load, Hepatocellular carcinoma, Late recurrence, Hepatic inflammatory activity